Right warfarin dose determined by 3 genes

March 20, 2009 -- Researchers at Uppsala University, together with colleagues at the
Karolinska Institute and the Sanger Institute, have now found all the
genes the determine the dosage of the blood-thinning drug warfarin. The
findings are published in the scientific journal PLoS Genetics.

"We
have previously studied selected genes that can affect warfarin
treatment. Now that we have gone in and scanned the entire genome, we
see that the two most important genes are among those we previously
singled out," says Mia Wadelius, a researcher at Uppsala University,
and one of the scientists behind the study.

She also says that this is the first truly large warfarin study in
which all genes were reviewed at the same time. More than 1,000
warfarin patients and roughly 370,000 gene variants, covering the
entire human genome, were studied.

"The adequate warfarin dosage
for a patient is determined by three genes: VKORC1, CYP2C9, and CYP4F2.
This is a step forward for a large group of patients, because it will
be easier to determine the dosage, and the treatment will be less
risky," says Mia Wadelius.

Patients vary in their sensitivity to
warfarin, which makes treatment initially a risky balancing act between
bleeding and blood clots. Mia Wadelius says that the variation is great
among patients, sometimes up to a difference of twenty times. But now
that researchers have managed to identify which genes underlie this
variation, it will be possible to predict different patients' needs for
warfarin more precisely, rendering treatment safer. The next step is to
look for markers for bleeding.

"We will continue to look for
genetic variants that influence the risk of bleeding, which can be a
reaction to warfarin treatment, though a rare one. The findings of the
Swedish study will be combined with those from a British study in order
to attain a sufficiently robust analysis of risks of bleeding," says
Mia Wadelius.